Project Summary Abstract The interdisciplinary research team at Integrated LLC has addressed a significant clinical need by developing a nanotech-bioactive water-based surface coating for titanium and titanium alloy based implants based on their advances in nanotechnology, stem cell biology. Our recently published data show that several of our peptides bind selectively and with high affinity to titanium and titanium alloys that are now used for dental implants and for correction of axial and craniofacial skeletal bone defects and joint replacements. Using this implant surface binding peptide as an anchor in combination with another small protein molecule enables us to introduce a bioactive function. Here we chose as a proof of concept, a small molecule we discovered that transiently activates the Wnt pathway for osteogenesis. Other bioactive functions such as an anti-microbial to control biofilms is also envisioned. This technology is water-based and the bifunctional small molecule approach serves to control the presentation of the biologically active peptides or protein at the implant interface to ensure cellular bioactivity. This promising nanotech-bioactive coating technology is designed to improve outcomes for all patients, including those challenged with advanced age or systemic diseases that are not now candidates for implants because of their high risk status. The coating also builds on the success of titanium surfaces to activate Wnt signals. Building upon the team`s accumulated expertise in bio- nanotechnology, materials science, stem cell biology, osteogenesis, and craniofacial biology, we developed peptides that mimic the characteristics of a biological surface on titanium or titanium alloy implantable material surfaces, thereby producing a biomimetic hard-soft interface that promotes cell attachment, while simultaneously directing the differentiation of the attached cells to osteogenic lineages in a single step. Our premise is that through the design of a self-organized bioactive interface on the implant surface we can further activate the canonical Wnt signaling pathway to direct the differentiation of stem cells to osteogenic lineages and improve osteointegration. Additionally, the coating can be used to re-treat previously placed implants that are failing due to bone loss from peri-implantitis to extend their useful life. Aim 1. Characterize the stability and temporal capacity of our biomimetic interface to retain Wnt signaling in vivo using a rabbit model well known to the implant industry.